The purpose of this study is to elucidate the relationship between ischemia stroke, stroke risk factors, infectious and inflammatory processes act as a "triggering" event, substantially increasing the likelihood of ischemic stroke in individuals placed at long-term risk by risk factors such as hypertension, diabetes and smoking. We will perform a 1:2 case-control study of 225 acute patients sustaining initial ischemic stroke compared to 450 matched stroke-free controls to estimate the relative risk of initial ischemic stroke due to recent infection- inflammation. Possible interactions between infection-inflammation and long-term risk factors. We will compare the endothelial-dependent hemostasis findings of stroke patients with infection-inflammation to stroke patients without infection-inflammation and to controls. We will also compare endothelial-dependent hemostasis finding for stroke-free subjects with and without stroke risk factors. Cases and their matched controls will be studied twice: immediately after the stroke and one month later. Hemostasis studies include a new assay for the important circulating anticoagulant activated proteins C as well as fibrinolytic (tissue plasminogen activator and plasminogen activator inhibitor-1) antigen and activity. We will analyze levels of circulating cytokines (including tumor necrosis factor-alpha) and infection serologies. Information generated by this project should lead to novel strategies in stroke prevention that will provide an important supplement to reduction or control of long-term stroke risk factors.